Wednesday, December 11, 2013

ASH 2013 - Chronic Infection, MGUS, & Myeloma

Paper 3116: Chronic Infection, a Neglected Cause Of Development Of Monoclonal Gammopathy Of Undetermined Significance (MGUS) and Myeloma

According to this French paper, it is well known that certain chronic infections can cause lymphomas and chronic leukemia, because the infection annoys the cells until they ultimately make a mistake and become malignant (my words - theirs are undoubtedly more clinically correct but well above my pay grade).  Apparently, something similar can happen to our plasma cells, turning them into malignant myeloma cells.

Indeed, the International Myeloma Foundation says "Several studies have linked myeloma to HIV, hepatitis, herpes virus infections (especially herpes virus 8), Epstein Barr Virus (EBV), as well as new 'stealth adapted' viruses such as mutated cytomegalovirus (CMV)."  The studies show that people with those infections are somewhat more likely than average to develop MGUS or myeloma.

Realistically, though, what is the risk for any one person?  The French researchers examined the question another way.  Since specific plasma cells are engineered (by our bodies) to attack specific threats, they tested the malignant cells, by examining the monoclonal immunoglobulins (M-spikes) that they produce, to see what threat they were designed to fight.  They tested the M-spike of 101 patients for reaction against eight different viruses and bacteria, and found that 23% of the patients' cells were specific for HCV (hepatitis C), EBV, or H. Pylori, a bacterium implicated in chronic stomach ulcers.  Any of the three infections can be present without symptoms.  For these 101 patients, no reaction was detected against the other five threats which, by the way, included CMV.

The authors propose: "Efforts should be made to identify the subsets of patients with (M-spikes) specific for HCV, EBV and H. Pylori, preferably at the MGUS stage, as anti-infection treatment is expected to cure MGUS and prevent progression toward myeloma."

A possible cure for MGUS and prevention of myeloma for some patients - wishful thinking?  I'm not a doctor, but I believe that H. Pylori can usually be cured with appropriate antibiotics.  I doubt that a cure is available for either HCV or EBV, but perhaps there are treatments which could reduce their impact on the immune system.

Should doctors be testing to identify patients with M-spikes specific to those infections?  Is it possible that, for some people with symptomatic myeloma, these infections could even cause further mutations of already-malignant myeloma cells, thereby assisting that myeloma in its deadly quest to eventually defeat every treatment?  Can anyone add more information?

Tuesday, December 10, 2013

ASH 2013 - Maintenance Matters

Paper 2: Initial Phase 3 Results Of The First (Frontline Investigation Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) In Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible For Stem Cell Transplantation (SCT)

The title suggests a comparison of Revlimid with low-dose dexamethasone, called Rd, and an old therapy consisting of melphalan, prednisone, and thalidomide, called MPT.  That comparison is significant in many parts of the world, where MPT is a standard of care for older patients, but MPT is rarely used now in the USA because doctors have newer drugs such as Revlimid, Velcade, Kyprolis and Pomalyst available, and know that those will perform better, even (especially?) in an older population.  This study confirms again that they are correct - Rd thoroughly trounces MPT.

For those of us seniors with access to Revlimid, though, this study clearly demonstrates the advantage of Revlimid maintenance after initial therapy.  It studied 1,623 newly-diagnosed myeloma patients over age 65 or ineligible for transplant, in three study arms: (A) Rd until disease progression; (B) Rd for 72 weeks or progression; and (C) MPT for 72 weeks or progression.

Some results for patients on continuous Rd versus those on 72-week Rd:
  • Median progression-free survival: 26 months versus 21 months.
  • Four-year overall survival: 59% versus 51%.
As time goes on, I would expect the difference in survival to grow.  If this were me, I sure would want to stay on the Revlimid continuously, rather than leave it after a year and a half.

Oh wait, it IS me!  I'm on a study of Pomalyst, in the same family of drugs as Revlimid, and it has kept my cancer under control for five and a half years now.  My study initially included low-dose Dex, just like this study, but my Dex was gradually reduced to zero over about 80 weeks.  For all practical purposes I have been on maintenance, using Pomalyst as a single agent, for at least four years.  During my study I have been able to run 50 marathons, so maintenance has offered a good quality of life.

Monday, December 9, 2013

ASH 2013 - Skip the Transplant

ASH is the American Society of Hematology, which has its annual meeting in early December each year, called the ASH Conference, or just ASH.  I will be blogging on several topics, but this one, though it is "just" a poster talk and not an oral presentation, seems extremely important because it suggests a change in the standard of care for newly-diagnosed patients.

Paper 3180: Lenalidomide and Dexamethasone Alone Is Equivalent To Lenalidomide and Dexamethasone With Autologous Stem Cell Transplant In Newly Diagnosed Multiple Myeloma: Interim Study Results Of a Randomized Trial.

The authors are from Columbia University and two other major universities.  Their small study has two arms: (1) Revlimid/dexamethasone (Rev/Dex), followed by autologous stem cell transplant (ASCT), then followed by Revlimid maintenance; and (2) The same Rev/Dex treatment and Rev maintenance, but without the transplant.  Here are some of the results:
  • More patients on the ASCT arm responded to treatment, 96% versus 77%.  No surprise.  Those who did not respond went off study and are not included in the statistics reported below.
  • Patients on the ASCT arm had a median progression-free survival of 17.0 months, versus 25.2 months for the Rev/Dex-only arm.  That's right - I don't have it backward.
  • Similarly, patients in the ASCT arm have a median overall survival (OS) of 57.6 months, while the OS for the other arm has not been calculated yet because more than half are still alive.
Needless to say, this is a startling result, because the up-front ASCT preceded by Rev/Dex or some other induction is still thought by many doctors to be the standard of care.  The authors are careful to downplay the obvious conclusions, however, saying that the study is small (47 patients total) and the follow-up short.  They go so far as to say that the PFS and OS differences between the two arms are "not statistically significant," presumably because of the small study size.

I have other caveats:
  • Previous studies have shown that more-aggressive treatment can benefit high-risk patients, and I do not see any effort in this study to identify those patients for separate evaluation or to remove their results from the overall calculations.
  • This is a study of newly diagnosed patients, and the results may not be at all relevant to previously-treated patients, especially to patients looking toward a second transplant.
  • Some of the numbers do not make sense to me.  For example, the authors say that only four patients have died in the ASCT arm, out of 25, yet they have computed a median OS.  I am missing something and did not have a chance to speak to the presenters.
  • I invite comments!  Perhaps someone can explain.
  • Other studies have shown that other frontline treatments may be even more effective than Rev/Dex, such as Kyprolis/Rev/Dex, followed by Rev maintenance.
My suggestion to any newly-diagnosed patient whose doctor is recommending a transplant:  Ask your doctor if s/he has read this abstract, or better yet the full paper.  If not, wait until s/he has read it.  Then ask why the results do not apply in your case.

For that matter, I believe that a transplant recommendation always calls for a second opinion anyway.  No matter what anyone says, a transplant is rough medicine with lifelong implications.